Download PDF
Synlett 2022; 33(01): 62-65
DOI: 10.1055/a-1672-3000
letter

First Total Synthesis of the Marine-Derived Anti-inflammatory Natural Product (–)-Herdmanine D through a Steglich Esterification

Pankaj Sharma
a   Organic Synthesis Research Laboratory, ARSD College, University of Delhi, New Delhi-110021, India
,
Nutan Sharma
b   Department of Chemistry, Faculty of Science, Shree Guru Gobind Singh Tricentenary University, Gurugram, Haryana, India
,
Gunjan Kashyap
a   Organic Synthesis Research Laboratory, ARSD College, University of Delhi, New Delhi-110021, India
,
Sunita Bhagat∗
a   Organic Synthesis Research Laboratory, ARSD College, University of Delhi, New Delhi-110021, India
› Author AffiliationsThe authors are grateful to SERB, Department of Science and Technology, India, for providing financial support (Sanction order no. SB/S1/OC-91/2013)
› Further Information
    Permissions and Reprints All articles of this category


Abstract

An efficient and regioselective route for the first total synthesis of the antiinflammatory marine natural product (–)-herdmanine D, with an excellent overall yield of 18%, is described. A key feature of the synthetic strategy is a Steglich esterification of regioselectively constructed 6-bromo-5-methoxy-1H-indole-3-carboxylic acid with protected l-tyrosine. The formation of the l-isomer was confirmed through measurement of the optical activity. The current strategy paves the way for the construction of diverse analogues of (–)-herdmanine D for drug development.

Key words

herdmanine D - regioselectivity - total synthesis - indoles - pharmaceutical chemistry

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1672-3000.
  • Supporting Information


Publication History

Received: 07 September 2021

Accepted after revision: 18 October 2021

Accepted Manuscript online:
19 October 2021

Article published online:
11 November 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References and Notes

  • 4 Blunt JW, Copp BR, Keyzers RA, Munro MH, Prinsep MR. Nat. Prod. Rep. 2015; 32: 116
    CrossrefPubMedSearch in Google Scholar
  • 5 Agrawal S, Acharya D, Adholeya A, Barrow CJ, Deshmukh SK. Front. Pharmacol. 2017; 8: 828
    CrossrefPubMedSearch in Google Scholar
  • 6 Rangel M, de Barcellos Falkenberg M. J. Coastal. Life Med. 2015; 3: 421
    Search in Google Scholar
  • 8 Sharma P, Sharma N, Kashyap G, Bhagat S. Synth. Commun. 2020; 50: 719
    CrossrefSearch in Google Scholar
  • 9 (–)-Herdmanine D A solution of LiOH (0.13 g, 5.0 equiv) in H2O (2 mL) was added slowly to a stirred solution of ester 7 (0.5 g, 1.0 equiv) in MeOH (2 mL), and the mixture was stirred for 4 h at rt. When the reaction was complete (TLC), the mixture was concentrated under reduced pressure and acidified with 1 N aq HCl to pH 2. The solid that precipitated was collected by filtration on a sintered funnel, washed with ice-cold H2O, and then dried under a high vacuum to give a light-brown solid; yield: 0.18 g (41%); mp 210–215 °C; [α]D 23 –20.3. 1H NMR (400 MHz, DMSO-d 6): δ = 12.96 (br s, 1 H, –COOH), 12.36 (br s, 1 H, –NH), 9.22 (s, 1 H), 8.76 (s, 1 H), 8.46–8.43 (d, J = 9 Hz, 2 H), 7.83 (s, 1 H), 7.65–7.63 (d, J = 6 Hz, 2 H), 7.37–7.35 (d, J = 6 Hz, 2 H). 4.02–3.94 (m, 1 H), 2.79–2.75 (m, 2 H). 13C NMR (100 MHz, DMSO-d 6): δ = 176.47, 164.72, 149.21, 140.54, 136.99, 132.84, 129.65, 127.44, 123.74, 120.54, 117.34, 111.51, 108.30, 106.89, 104.67, 103.70, 57.38, 36.88. HRMS (ESI): m/z [M + H]+ calcd for C18H15BrN2O5: 418.0164; found: 418.0170.